Introduction: Type 2 diabetes mellitus (T2DM) is a group of metabolic disorder and is an independent risk factor for cardiovascular disease and dyslipidaemia. Patients with T2DM have dyslipidaemia at wavering degrees, characterised by increased levels of triglyceride and low-density lipoprotein-cholesterol and decreased levels of high-density lipoprotein (HDL)-cholesterol. In the present study, we evaluated glycated haemoglobin (HbA1c) as a marker of circulating lipids in patients with T2DM. Methods: Two hundred and thirty-nine patients with T2DM were enrolled for the study. A detailed biochemical and lipid profile was done for all patients. Results: Of 239 cases, 96 (40%) were male and 143 (60%) were female. Of 239 patients, 53 (22%) patients with T2DM had controlled glycaemia (HbA1c <6.5) and 186 (78%) patients had uncontrolled glycaemia (HbA1c ≥6.5). Pearson's correlation of HbA1c with all lipid parameters was statistically significant. HbA1c, however, had an inverse correlation with HDL and had a significant direct correlation with fasting blood glucose. Conclusion: The study reveals that HbA1c is not only a reliable glycaemic index but can also be used as an important indicator of dyslipidaemia in patients with T2DM.

Type 2 diabetes mellitus (T2DM) is a group of metabolic disorder that is characterised by hyperglycaemia resulting from insulin resistance in the target organ with hyperinsulinaemia initially and loss of beta islet cell in later stages which leads to relative insulin deficiency.[1] At present, the incidence of diabetes has exceeded what was expected 12 years ago and it is expected to increase further. Prevention of diabetes is of utmost importance for the primary care clinicians. The patient can be asymptomatic for a long time before the diagnosis is made.[2] Epidemiological studies have recognised that T2DM is an independent risk factor for cardiovascular disease (CVD), and it supplements the effect of common risk factors such as smoking, hypertension and dyslipidaemia.[3] There is a high risk of CVD in people with T2DM while CVD deaths represent the top killer in this population.[4] Serum lipids are frequently abnormal and are likely to contribute to the risk of coronary artery disease.[5] Worsening of glycaemic control deteriorates lipid and lipoprotein abnormalities and particularly of diabetes mellitus (DM).[6] It is documented that most patients with T2DM have dyslipidaemia at wavering degrees, characterised by increased levels of triglycerides (TGs) and low-density lipoprotein (LDL) and decreased levels of high-density lipoprotein (HDL).[7] Hence, the association between serum lipid profile and glycated haemoglobin (HbA1c) was evaluated in the present study, hypothesising that early detection and treatment of lipid abnormalities can minimise the risk of atherogenic accident in patients with T2DM.

Methods

The study included 239 randomly selected, clinically confirmed T2DM patients from January 2016 to June 2016. All the cases were recruited from outpatient department (OPD) and inpatient department (IPD) of the Department of Postgraduate Department of Internal Medicine, Government Medical College, Srinagar, and associated Shri Maharaja Hari Singh Hospital, Srinagar, India. The American Diabetic Association criteria were used in defining DM.[8] ATP3 National Cholesterol Educational Program (NCEP) guidelines were used in defining dyslipidaemia.[9] Patients taking multivitamin supplementation, patients treated with lipid-lowering drugs at the time of referral or having hepatic, renal or metabolic bone disorders, including parathyroid-related problems, patients with history of haemoglobinopathies were excluded from the study. Those patients having history of malabsorption syndromes such as celiac disease or active malignancy or with active infection were also excluded from the study. The study participants were asked to complete a generalised questionnaire that contains demographic information including past and present medical history.

Biochemical analysis of blood samples

Overnight fasting venous blood samples were collected from the patients in ethylenediaminetetraacetic acid -containing tubes using standardised protocol and equipment. They were separated into two samples: the first sample containing whole blood for the measurement of HbA1c and the other plasma specimen was used for fasting blood glucose (FBG) and lipid profile levels (Abbott C4000, USA).

Laboratory investigations

Estimation of FBG was done using glucose oxidase-peroxidase method [10]

Written informed consent (in language they can best understand) was obtained before collecting data and blood sample. Only those individuals, who volunteered to participate in the study, were selected and the data were kept confidential. The study did not impose any financial burden on the study participants and the institute; therefore, the study was ethically justified.

Data management and statistical analysis

During data collection, completed questionnaires were checked regularly to rectify any discrepancy, logical errors or missing information. The data entry was carried out using Microsoft Office Excel worksheet and then exported to statistical software and analysed using appropriate statistical tests using Statistical Package for Social Sciences (SPSS vs. 21 for Mac, IBM Inc., Chicago, IL, USA). Mean ± standard deviation was calculated by applying Student's t-test. The correlation was calculated using the formula of Pearson correlation coefficient between HbA1c, FBS and lipid profile. The obtained results were analysed and inferences were drawn from these. P≤ 0.05 was considered statistically significant.

Results

Two hundred and thirty-nine patients with T2DM were enrolled for the present study. These included both drug naïve and follow-up cases who attended the Department of Medicine (OPD/IPD) of our tertiary care centre. Of 239 cases, 96 (40%) were male and 143 (60%) were female. The mean age of males was 53.32 ± 12.4 years and that of females was 50.3 ± 14.0 years (P = 0.08). The details of biochemical parameters of our patients are shown in [Table 1].

The impact of the glycaemic control was evaluated by categorising patients into two groups. Of 239 patients, 53 (22%) patients with T2DM had controlled glycaemia (HbA1c <6.5) and 186 (78%) patients had uncontrolled glycaemia (HbA1c ≥6.5). The biochemical details of these patients are shown in [Table 2].

Pearson's correlation of HbA1c with all lipid parameters except VLDL was statistically significant as shown in [Table 3]. HbA1c, however, had an inverse correlation with HDL and had a significant direct correlation with FBG (Pearson correlation 0.247; P ≤ 0.001).

In the present study, we evaluated the pattern of lipid profile parameters in 239 diabetic patients and its correlation with HbA1c. The biochemical parameters did not show any significant relation between males and females except for the TGs, which was statistically significant between the two groups. Further, the study participants were categorised into two groups based on the glycaemic control (i.e., with HbA1c ≥6.5 and HbA1c <6.5). The lipid parameters and FBG were significant between the two groups. The general increased levels of serum lipids in DM patients may be mainly attributed to increase in the mobilisation of free fatty acids from fat depots; insulin affects the liver apolipoprotein production. It regulates the enzymatic activity of lipoprotein lipase and cholesteryl ester transfer protein. All these factors are likely cause of dyslipidaemia in T2DM.[14],[15],[16]

The percentage of HbA1c reflects the glycaemic control of a patient. The complications of diabetes and control trial established HbA1c as the gold standard of glycaemic control. Lowering HbA1c has been shown to reduce microvascular complications of diabetes, and if implemented soon after the diagnosis of diabetes, it is associated with long-term reduction in macrovascular disease.[17],[18]

A major risk factor for the development of cardiovascular events in diabetes is dyslipidaemia. The classic features of diabetic dyslipidaemia are high plasma TG concentration, low HDL component and increased concentration of small, dense LDL particles. The LDL can be normal in diabetes. The LDL found in diabetes is small, dense molecule which is highly atherogenic. Diabetics display enhanced LDL oxidizability, and there is increased rate of atherosclerosis. There is local release of hypochlorous acid from myeloperoxidase, which interacts with HDL molecule and decreases its action which is reverse cholesterol transport. There are various alterations in small, dense LDL molecule which make it more atherogenic such as reduced LDL receptor affinity, greater propensity for transport into the subendothelial space, increased binding to arterial wall proteoglycans.[19]

The NCEP identified elevated LDL as a primary risk factor for coronary heart disease.[20] Recently, molar ratio log TG/HDL popularly known as atherogenic index of plasma has been proposed as a predictive marker for plasma atherogenicity and positively correlated with CVD risk.[21] HbA1c can also be used as a potential biomarker for predicting atherogenicity in patients with T2DM. In the present study, positive and significant correlation between HbA1c and lipid parameters was observed, and HbA1c had inverted significant correlation with HDL. A highly significant correlation between HbA1c and FBG in our study is similar to various previous studies.[20],[22],[23],[24]

Improving glycaemic control can substantially reduce the risk of cardiovascular events in diabetics. It has been estimated that reducing HbA1c levels by 0.2% could lower the mortality by 10%.[25] Based on our results, we assume that HbA1c can be used as an important marker to predict the dyslipidaemic conditions in patients with T2DM. However, further studies based on larger patient numbers are needed on the role of HbA1c as a marker for dyslipidaemia in T2DM.

Conclusion

Our study reveals that HbA1c is not only a reliable glycaemic index but also can be used as an important indicator of dyslipidaemia in patients with T2DM.

Acknowledgements

We thank all the technical staff of our laboratory for their help and support.